Innervation of Meissner's corpuscles and Merkel -cells by transplantation of embryonic dorsal root ganglion cells after peripheral nerve section in rats.

Transplantation of embryonic motor neurons has been shown to improve motor neuron survival and innervation of neuromuscular junctions in peripheral nerves. However, there have been no reports regarding transplantation of sensory neurons and innervation of sensory receptors. Therefore, we hypothesized that the transplantation of embryonic sensory neurons may improve sensory neurons in the skin and innervate Merkel cells and Meissner's corpuscles. We obtained sensory neurons from dorsal root ganglia of 14-day rat embryos. We generated a rat model of Wallerian-degeneration by performing sciatic nerve transection and waiting for one week after. Six months after cell transplantation, we performed histological and electrophysiological examinations in naïve control, surgical control, and cell transplantation groups. The number of nerve fibers in the papillary dermis and epidermal-dermal interface was significantly greater in the cell transplantation than in the surgical control group. The percent of Merkel cells with nerve terminals, as well as the average number of Meissner corpuscles with nerve terminals, were higher in the cell transplantation than in the surgical control group, but differences were not significant between the two groups. Moreover, the amplitude and latency of sensory conduction velocity were evoked in rats of the cell transplantation group. We demonstrated that the transplantation of embryonic dorsal root ganglion cells improved sensory nerve fiber number and innervation of Merkel cells and Meissner's corpuscles in peripheral nerves.

Muscle spindle reinnervation using transplanted embryonic dorsal root ganglion cells after peripheral nerve transection in rats.

OBJECTIVES: Muscle spindles are proprioceptive receptors in the skeletal muscle. Peripheral nerve injury results in a decreased number of muscle spindles and their morphologic deterioration. However, the muscle spindles recover when skeletal muscles are reinnervated with surgical procedures, such as nerve suture or nerve transfer. Morphological changes in muscle spindles by cell transplantation procedure have not been reported so far. Therefore, we hypothesized that transplantation of embryonic sensory neurons may improve sensory neurons in the skeletal muscle and reinnervate the muscle spindles. MATERIALS AND METHODS: We collected sensory neurons from dorsal root ganglions of 14-day-old rat embryos and prepared a rat model of peripheral nerve injury by performing sciatic nerve transection and allowing for a period of one week before which we performed the cell transplantations. Six months later, the morphological changes of muscle spindles in the cell transplantation group were compared with the naïve control and surgical control groups. RESULTS: Our results demonstrated that transplantation of embryonic dorsal root ganglion cells induced regeneration of sensory nerve fibre and reinnervation of muscle spindles in the skeletal muscle. Moreover, calbindin D-28k immunoreactivity in intrafusal muscle fibres was maintained for six months after denervation in the cell transplantation group, whereas it disappeared in the surgical control group. CONCLUSIONS: Cell transplantation therapies could serve as selective targets to modulate mechanosensory function in the skeletal muscle.

Upper extremity disability is associated with pain intensity and grip strength in women with bilateral idiopathic carpal tunnel syndrome.

BACKGROUND: The upper extremity disability in patients with carpal tunnel syndrome (CTS) is related to dysfunction due to the median nerve damage. However, there is no report on which dysfunctions affect the upper extremity disability. PURPOSE: This study aimed to investigate which clinical factors influence upper extremity disability in women with CTS. METHODS: We analyzed 60 hands of women with bilateral idiopathic CTS. Upper extremity disability was assessed using Hand10, a validated and self-administered tool. Pain intensity was measured using the Japanese version of the Short-Form McGill Pain Questionnaire (SF-MPQ-J). We performed nerve conduction studies, assessed physical and psychological parameters, and collected demographic data. Physical parameters comprised grip strength, pinch strength, tactile threshold, static 2-point discrimination sensation, and severity of numbness. Psychological parameters include depression, pain anxiety, and distress. RESULTS: The bivariate analysis revealed that Hand10 was significantly correlated with age, symptom duration, SF-MPQ-J, grip strength, pain anxiety, and distress. Multiple regression analysis demonstrated that SF-MPQ-J and grip strength were related to Hand10 score. CONCLUSIONS: Pain intensity and grip strength were dysfunctions affecting the upper extremity disability in women with bilateral idiopathic CTS. Rehabilitation approaches for CTS should be considered based on the adaptive activities of the neural networks.

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 µm2 , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle.

Recovery function of somatosensory evoked brain response in patients with carpal tunnel syndrome: A magnetoencephalographic study.

OBJECTIVE: The recovery function of somatosensory evoked magnetic fields (SEFs) was recorded to investigate excitatory and inhibitory balance in the somatosensory cortex of patients with carpal tunnel syndrome. METHODS: SEFs were recorded in patients and controls. Recordings were taken following median nerve stimulation with single and double pulses with interstimulus intervals of 10-200ms. The root mean square for the N20m component following the second stimulation was analyzed. SEFs following stimulation of the first and middle digits were also recorded and the location for the equivalent current dipoles was estimated in three-dimensional planes. RESULTS: Distances on the vertical axis between the equivalent current dipoles for the first and third digits were shorter in patients than in control participants. The root mean square for the N20m recovered earlier in patients compared to controls; this was statistically significant at an interstimulus interval of 10ms. There was no relationship between N20m recovery and the equivalent current dipole location in the primary somatosensory cortex. CONCLUSIONS: Carpal tunnel syndrome was associated with functional disinhibition and destruction of the somatotopic organization in the primary somatosensory cortex. SIGNIFICANCE: Disinhibitory changes might induce a maladaptation of the central nervous system relating to pain.

Transplantation of embryonic motor neurons into peripheral nerve combined with functional electrical stimulation restores functional muscle activity in the rat sciatic nerve transection model.

Reinnervation of denervated muscle by motor neurons transplanted into the peripheral nerve may provide the potential to excite muscles artificially with functional electrical stimulation (FES). Here we investigated whether transplantation of embryonic motor neurons into peripheral nerve combined with FES restored functional muscle activity in adult Fischer 344 rats after transection of the sciatic nerve. One week after sciatic nerve transection, cell culture medium containing (cell transplantation group, n = 6) or lacking (surgical control group, n = 6) dissociated embryonic spinal neurons was injected into the distal stump of the tibial and peroneal nerves. Electrophysiological and tissue analyses were performed in the cell transplantation and surgical control groups 12 weeks after transplantation, as well as a in naïve control group (n = 6) that received no surgery. In the cell transplantation group, ankle angle was measured during gait, with and without FES of the peroneal nerve. Ankle angle at mid-swing was more flexed during gait with FES (26.6 ± 8.7°) than gait without FES (51.4 ± 12.8°, p = 0.011), indicating that transplantated motor neurons in conjunction with FES restored ankle flexion in gait, even though no neural connection between central nervous system and muscle was present. These results indicate that transplantation of embryonic motor neurons into peripheral nerve combined with FES can provide a novel treatment strategy for paralysed muscles. Copyright © 2013 John Wiley & Sons, Ltd.

Successful transplantation of motoneurons into the peripheral nerve depends on the number of transplanted cells.

Transplantation of motoneurons (MN) into the peripheral nerve to provide a source of neurons for muscle reinnervation, termed motoneuron integrated striated muscle (MISM), may provide the potential to restore functional muscle activity, when combined with computer-programmed functional electrical stimulation (FES). The number of MNs required to restore innervation to denervated muscles in adult Fischer 344 rats was investigated by comparing two groups, one transplanted with 2 × 10(5) cells (group A) and the other with 1 × 10(6) cells (group B). Twelve weeks after transplantation, electrophysiological analysis, muscle function analysis, and tissue analysis were performed. The mean motor nerve conduction velocity was faster (12.4 ± 1.0 m/s vs. 8.5 ± 0.7 m/s, P = 0.011) and the mean amplitude of compound muscle action potential was larger (1.6 ± 0.4 mV vs. 0.7 ± 0.2 mV, P = 0.034) in group B. The dorsiflexed ankle angle was larger in group B (27 ± 5° vs. 75 ± 8°, P = 0.02). The mean myelinated axon number in the peroneal nerve and the proportion of reinnervated motor end plates were also greater in group B (317 ± 33 vs. 104 ± 17, 87.5 ± 3.4% vs. 40.6 ± 7.7%; P < 0.01, respectively). When sufficient MNs are transplanted into the peripheral nerve, MISM forms functional motor units. MISM, in conjunction with FES, provides a new treatment strategy for paralyzed muscles.